Ischemic Brain Disease Research Articles

Importance of normolipidemic dyslipoproteinemia in development of ischemic brain disease

Importance of normolipidemic dyslipoproteinemia in development of ischemic brain disease

Importance of hemispheric localization of ischemic brain disease

Importance of hemispheric localization of ischemic brain disease

298 Role of hemispheric localization of ischaemic brain disease in development of cardiac complications

298 Role of hemispheric localization of ischaemic brain disease in development of cardiac complications

Ischemia and reperfusion in pancreas.

Ischemic diseases of heart and brain are the primary causes of mortality in industrialized nations. The ischemic injury with the consecutive reperfusion is responsible for the disturbance of microcirculation with ensuing tissue damage and organ dysfunction. Recent evidence suggests that oxygen-derived free radicals and activated polymorphonuclear leukocytes produced in ischemic tissue are instrumental in the development of ischemic cell injury. In pancreas, ischemia/ reperfusion is proposed as a potentially damaging factor accounting in part for the pathogenesis of acute pancreatitis. Apart from ischemia/reperfusion injury, the kallikrein-kinin system mediates acute inflammation associated with enhanced capillary permeability and accumulation of polymorphonuclear leukocytes, cardinal features of ischemia/reperfusion injury also in acute pancreatitis. Therefore, it seems reasonable to use bradykinin-antagonists to influence postischemic reperfusion injury of the pancreas. In the following, we describe the pathophysiology of ischemia/reperfusion injury with special reference to the pancreatic microcirculation and morphological changes as observed in a model of complete and reversible ischemia. Furthermore, we will discuss the effects of two bradykinin-antagonists (HOE 140 and CP-0597) on functional integrity of the pancreas after ischemia/ reperfusion.

Nuclear disintegration as a leading step of glutamate excitotoxicity in brain neurons.

Recent studies on ischemic brain disease in vivo and glutamate excitotoxicity in vitro suggest that apoptosis may play a role in excitotoxic neuronal death. To examine the possible involvement of apoptosis in glutamate excitotoxicity, we studied an early process of morphological changes in rat cortical neurons exposed to 1 mM glutamate. Observations under Nomarski optics combined with a digital image processor revealed a rapid change in the nucleus followed by a cellular swelling. The nucleus increased in granularity and swelled in 5 min, then became liquefied in 30 min. The cell body swelled slowly in 15-45 min. These changes could be prevented by treatment of the neuron with MK-801 (dizocilpine maleate), a blocker of N-methyl-D-aspartate (NMDA) receptor-coupled ion channel. However, treatment of the neurons with N(G)-nitro-L-arginine (N-NORG), a nitric oxide synthase inhibitor, had no significant effect. Use of the in situ end-labeling technique for the demonstration of free 3'-hydroxyl ends revealed that DNA fragmentation took place within 1 hr after glutamate exposure. A change in intracellular Ca(2+) concentration was examined with fluo-3 under a confocal laser microscope. Application of 1 mM glutamate induced rapid Ca transients in the nucleus as well as in the cytoplasm. Both of these Ca responses were blocked by MK-801. These results indicate that glutamate excitotoxicity in the brain neuron does not fulfill morphological criteria of apoptosis, but suggest that the nuclear disintegration associated with DNA fragmentation is involved as a leading step in glutamate excitotoxicity.

Brain Ischemia: Basic Concepts and Clinical Relevance

Brain Ischemia was written by a clinician for clinicians with the express purpose of giving the practicing neurologist the scientific basis for understanding and exploiting new ideas and therapies for ischemic brain disease. The neurologist is no longer asked simply to see, examine, diagnose, then pass by the patient with symptomatic cerebral ischemia. Instead, he or she is consulted by primary care physicians to prevent or treat symptoms of cerebrovascular disease, interpret them in the context of systemic illnesses, and forecast their outcomes. Although the incidence of stroke has declined during the past 15 years, clinical interest in ischemic brain disease has grown dramatically, fueled by new understanding of its pathophysiology. Advances in molecular biology of cell membranes, neurotransmitter physiology, and mechanisms of cellular death challenge clinicians to reeducate themselves constantly or to risk using new therapies inappropriately or dangerously. This book succeeds well in organizing, presenting, and explaining the

Overexpression of Vascular Endothelial Growth Factor in the Avian Embryo Induces Hypervascularization and Increased Vascular Permeability without Alterations of Embryonic Pattern Formation

Vascular endothelial growth factor (VEGF)—also known as vascular permeability factor—has been implicated in the regulation of blood vessel formation, i.e., vasculogenesis and angiogenesis. High amounts of VEGF mRNA and protein have been detected during embryonic and tumor angiogenesis, but it remained unclear whether the level of VEGF correlated with the extent of vascularization in a given organ or tissue. We examined the role of VEGF and the high affinity, signal-transducing VEGF receptor-2 (flk-1) in the avian embryo. In a gain of function transgene-like approach the retroviral expression vector RCAS was used to increase the level of quail VEGF during critical periods of avian limb bud growth and morphogenesis. In contrast to basic fibroblast growth factor, which recently was demonstrated to induce morphogenetic alterations when overexpressed in this system, overexpression of VEGF in the limb bud exclusively resulted in hypervascularization as reflected by an increase in vascular density. However, cartilage expressing the construct was not vascularized prematurely. Thus hypervascularization was probably due to the augmentation of the VEGF signaling mechanism in a permissive environment. In addition to hypervascularization, vascular permeability was dramatically increased, leading to local and in some cases to general edema. This is the first indication of a link between the functions of VEGF as a vascular growth factor and as a permeability factor. VEGF receptor-2 (flk-1) was found to be upregulated only in those areas where VEGF was overexpressed. This implies a positive feedback system of the VEGF receptor on its own synthesis and would provide a basis for a paracrine system in which ligand concentration is critical for the extent of tissue vascularization. Our results show that the VEGF/VEGF-receptor system is specific and sufficient for the formation of new blood vessels. They also have implications for somatic gene therapy of diseases which are characterized by a lack of blood vessels such as chronic ischemic diseases of heart and brain.

Magnetic resonance angiographic findings in vertiginous patients with slow vertebrobasilar blood flow.

To investigate arterial lesions underlying slow vertebrobasilar blood flow (SBF) which appears as a high intravascular signal on proton-density images, we examined 35 vertiginous patients, 15 with SBF and 20 without, using magnetic resonance angiography. Vertebrobasilar dolichoectasia, segmental stenosis with elongation and diffuse narrowing of the vertebrobasilar arteries (VBA) were found in 4, 4 and 2 patients with SBF, respectively. In one patient with SBF, the thrombi that induced SBF seemed to have embolized to distal arteries. These abnormalities were not detected in patients without SBF, although 2 patients demonstrated aneurysm in the VBA. Because SBF is frequently associated with atherosclerotic arterial lesions, patients with SBF should be treated to prevent more severe ischemic brain disease.

Temporal Delta Wave and Ischemic Lesions on MRI

Abstract: The present study was designed to determine the clinical significance of a temporal low‐voltage irregular delta wave (TLID) on EEG. Among 808 EEG records examined during one year at our hospital, the TLID was commonly detected in patients with clinically diagnosed ischemic brain diseases such as multiple infarction. Subsequently, a relation of the TLID to ischemic lesions on MRI was examined in 50 elderly depressive patients. It was found that there was a close correlation between the occurrence of the TLID and small ischemic lesions on MRI (p<0.001). These results suggest that the TLID is a valuable indicator of minor ischemic changes of the brain.

Coupling of adenosine receptors to adenylate cyclase in postischemic rat brain

The potential usefulness of adenosine receptor stimulation in the therapy for ischemic brain disease is dependent upon retention of adenosine receptors and their transduction mechanisms after ischemia. The receptors most clearly associated with adenosine-dependent cerebral inhibition are the A 1-type (A 1-AR), which work via a G 1 protein to inhibit adenylate cyclase. In brain membranes from rats recoverin at various times after 15 min of complete cardiac arrest-induced ischemia, the levels of A 1-AR decreased temporarily to 60% of the control values. However, agonist affinities for A 1-AR, as well as guanine nucleotide-sensitive high-affinity binding, remain unchanged. The significant decrease of agonist affinities to A 1-AR produced by calcium depletion in control membranes was markedly attenuated after ischemia. Moreover, the A 1-AR agonist-induced inhibition of cAMP production parallels the decrease in these receptor numbers. It was blocked in the postischemic membranes but reverts to control levels upon extending the recovery period to one week after the insult. It is concluded that in addition to the lowering of the number of A 1-AR binding sites, the coupling of A 1 receptor activation to adenylate cyclase response is inhibited after ischemia, but not at the level of receptor-G 1 protein interaction.

Sustained decrease in brain regional blood flow after microsphere embolism in rats.

An experimental model that induces sustained ischemia and infarction may provide useful information relevant to prevention of the development of ischemic brain disease. The purpose of the present study was to elucidate the pathophysiological consequences of cerebral blood flow under sustained cerebral ischemia or oligemia and infarction in rats after microsphere embolism. We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 146 rats and determined the time course of changes in blood flow of the cerebral cortex, striatum, and hippocampus of both hemispheres by the hydrogen clearance method for a period of 28 days after the operation. Infarct area was determined by triphenyltetrazolium chloride staining and hematoxylin and eosin staining methods. Cortical and striatal blood flow of the right hemisphere of microsphere-injected rats was significantly decreased after the embolism, and this was sustained throughout the experiment. Hippocampal blood flow of the microsphere-injected hemisphere was also decreased on days 1 and 3 but tended to return toward control levels thereafter. In the left hemisphere, reduction in regional blood flow was detected in the cortex and hippocampus on day 1 and the striatum on day 3. A triphenyltetrazolium chloride-unstained area had developed by day 3 after the embolism. The extent of the area was similar to that on days 7 and 28. Microscopic examination revealed degenerative areas scattered mainly in the parietotemporal cortex, corpus callosum, hippocampus, thalamus, and lenticular nucleus of the embolized hemisphere, demonstrating the induction of widespread necrosis after embolism. Microsphere embolism resulted in a sustained decrease in regional blood flow and production of cerebral infarction in the brain regions of the microsphere-injected hemisphere.

Outcomes of Carotid Endarterectomy

Letters15 April 1991Outcomes of Carotid EndarterectomyCamilo R. Gomez, MDCamilo R. Gomez, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-8-703_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editors: The article by Brook and colleagues (1) contains serious methodologic flaws that make some of the findings questionable and others reprehensible.First, the outcome of the study is based on "appropriateness" of carotid endarterectomy. Nobody knows exactly for what patient, if any, this procedure is appropriate. The authors themselves recognize this in their introduction and yet analyze the data based on opinions expressed by consultants (2).Second, the issue of "illness-severity" is problematic. It is unclear to what illness the authors are referring: isolated carotid artery disease? cerebrovascular atherosclerosis? ischemic brain disease? and, if so, hemodynamic? embolic?...

MRS of ischemic/hypoxic brain disease.

Significant increases in magnetic field strengths and improvements in magnetic field homogeneity have made combined high-resolution magnetic resonance imaging (MRI) and multinuclear spectroscopy (MRS) feasible for investigating the relationship between biochemical and structural changes induced by ischemic brain disease. Magnetic resonance spectroscopy is the only noninvasive technique capable of measuring concentrations of high-energy phosphate metabolites, lactate, and other metabolically relevant compounds. Anticipated advances in localization of the volume of tissue from which spectra are obtained will enhance the clinical potential of MRS in the diagnosis of ischemic disease.

Antiphospholipid antibodies

Lupus anticoagulants and anticardiolipin antibodies, known collectively as antiphospholipid antibodies, are becoming established as markers for increased risk of thrombosis, including ischemic cerebrovascular disease. In this brief review, we highlight evidence for and against a pathogenetic role of these antibodies in ischemic brain disease and comment on currently available laboratory studies to detect them. Future research on the association of antiphospholipid antibodies with neurological disease should focus on establishing the pathogenicity of these antibodies, identifying groups at high risk for recurrent ischemic cerebrovascular events, and initiating prospective multicenter natural history and treatment protocols.

Predominant Left Hemisphere Metabolic Dysfunction in Dementia

Thirty-one patients with probable Alzheimer's disease and 11 patients with memory disorders, attributable to multiple cerebral infarctions, were studied using 18-F-fluorodeoxyglucose-positron emission tomography scans. Asymmetry in cerebral glucose metabolism within these diagnostic groups was assessed by comparison with the metabolic rates obtained in age-equivalent healthy control subjects. A significantly greater number of individuals in both patient groups exhibited predominant left rather than right hemisphere hypometabolism. In addition, for patients with Alzheimer's disease, the degree of asymmetry was not related to either the severity or duration of dementia. These findings could be explained by greater susceptibility of the left hemisphere to degenerative or ischemic brain disease, by a specific sampling effect, or most likely, by greater metabolic deficits resulting from left rather than right hemisphere impairment.

Revaluation of the Cervical Sympathectomy for Ischemic Brain Disease

Revaluation of the Cervical Sympathectomy for Ischemic Brain Disease

Evaluation of head trauma by computed tomography.

A wide spectrum of traumatic abnormalities has been demonstrated by computed tomography. CT findings in acute trauma range from cerebral edema and contusion to intracerebral or extracerebral hematoma, subarachnoid and intraventricular hemorrhage and varying combinations thereof. Late traumatic changes shown by CT include chronic subdural hygroma, post-traumatic infarct, and porencephaly and hydrocephalus. The latter findings are indistinguishable from changes resulting from degenerative or ischemic brain disease. Follow-up CT scanning elucidates the natural course of various traumatic lesions. Occasionally, it may uncover occult, delayed sequelae which can be remedied surgically before irreparable brain damage occurs.